Maybe it's an evil organization that wants to isolate Naruto. By making his family forget him, they hope to break Naruto's spirit and prevent him from becoming a powerful force in the ninja world. So they target his family's memories as a way to get to him.
Perhaps the main antagonist is a powerful and jealous shinobi. He sees Naruto's potential and the support he gets from his family. Out of envy, he uses a forbidden technique to make Naruto's family forget him, so that Naruto will be alone and more likely to fail in his ninja journey.
Maybe the main antagonist is a member of Naruto's own family who is power - hungry. This family member sees Naruto's growth to the Jounin level as a threat to their own position within the family. So, they manipulate the rest of the family into forgetting Naruto and excluding him from the family unit. They would stop at nothing to keep Naruto away and maintain their own power and influence.
Another possibility is that the antagonist could be a dark - side version of Naruto himself. The discovery of the forgotten bloodline could stir some dark desires within him. This internal struggle could be personified as a separate entity that tries to take over Naruto and use the power of the bloodline for evil. Naruto would then have to fight against this internal darkness as well as external threats who are also interested in his new - found power.
It could be a rogue ninja who has a vendetta against Shizune's family. This ninja might see Naruto as an obstacle in his path to revenge. He could target Naruto to get to Shizune and try to break their family - like bond.
Perhaps an old enemy of Naruto's who resurfaces and decides to target his family. This could be someone who was defeated by Naruto long ago but has now grown stronger and wants to cause harm to his loved ones. They might also see Kakashi as a threat in protecting the family.
Obviously Naruto himself would be a main character as the story is about him being forgotten by his family. His parents, if they are alive in this fanfiction, could also be important characters. They are the ones who are forgetting him, so their actions and reasons for this forgetfulness would be crucial to the story. And perhaps his friends like Sasuke and Sakura could also play important roles. They might be the ones to support Naruto when his family fails to do so, and they could also help him in his quest to figure out what's wrong with his family.
The mother's new partner. He doesn't want the forgotten daughter to be part of the family as he fears she will disrupt the new family dynamic he has been trying to build. He might use various means to keep her away from the family.
It could be a relative from his family who was behind the abandonment. Maybe they want to keep Naruto away from some family secret or power, and they will do anything to stop him from finding out the truth.
It could be Orochimaru. He has always been interested in powerful jutsus and Naruto's unique power as a Jinchuriki. He might have developed a new jutsu to make everyone forget Naruto so that he can capture him without interference for his own experiments.
It could be Orochimaru. He's always been interested in experimenting and causing chaos. Maybe he wants to use Naruto's parents' forgetfulness as a way to study the Uzumaki clan's mental state or something related to their chakra. He might see Naruto's vulnerability in this situation as an opportunity to get closer to his goals.
It could be a powerful ninja from another village who sees Naruto's godlike powers as a threat to his own plans of domination. Since Naruto is already feeling vulnerable due to his family leaving him, this antagonist might try to take advantage of his emotional state.